For the Consumer

Along with its needed effects, paroxetine (the active ingredient contained in Paxil CR) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking paroxetine:

Less Common

Agitation

chest congestion

chest pain

chills

cold sweats

confusion

difficulty with breathing

dizziness, faintness, or lightheadedness when getting up from a lying or sitting position

Some side effects of paroxetine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

The most common dose-dependent side effects associated with treatment discontinuation in clinical trials for the treatment of premenstrual dysphoric disorder with controlled-release paroxetine (the active ingredient contained in Paxil CR) 25 mg compared with 12.5 mg included nausea, somnolence, impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, and yawn.

The most common side effects associated with treatment discontinuation in the treatment of vasomotor symptoms in clinical trials included abdominal pain, attention disturbances, headache, and suicidal ideation.

In a placebo-controlled study in elderly patients with major depressive disorder, the most common side effects associated with treatment discontinuation of controlled-release paroxetine included nausea, headache, depression, and abnormal LFTs.

There may be adaptation to some side effects (such as nausea and dizziness) but not to others (such as dry mouth, somnolence, and asthenia) with continued therapy. Paroxetine is less likely than tricyclic antidepressants to be associated with dry mouth, constipation, and somnolence.[Ref]

Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.

Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.

Pooled results from clinical trials report hallucinations in 22 of 9089 patients who received paroxetine and 4 of 3187 patients who received placebo.[Ref]

Nervous system

Extrapyramidal symptoms such as akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, and oculogyric crisis have been associated with concomitant pimozide therapy.

Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin. Signs and symptoms associated with serotonin syndrome or neuroleptic malignant syndrome included agitation, confusion, diaphoresis, diarrhea, fever, hypertension, rigidity, and tachycardia, and were in some cases associated with concomitant use of serotonergic drugs.[Ref]

Metabolic

The results of one study appear to indicate that treatment with selective serotonin reuptake inhibitors (i.e., paroxetine (the active ingredient contained in Paxil CR) sertraline, citalopram) may cause an increase in serum total cholesterol, HDL cholesterol, and/or LDL cholesterol. However, additional studies are necessary to confirm these findings.

Numerous cases of hyponatremia have been reported following treatment with a selective serotonin reuptake inhibitor (SSRI). Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) via release of antidiuretic hormone.[Ref]

Other

Fatigue, malaise, and lethargy were very commonly reported in Phase 2 and 3 clinical trials with paroxetine (the active ingredient contained in Paxil CR) for treatment of vasomotor symptoms in postmenopausal women.[Ref]

There are several reports of priapism associated with paroxetine use. In cases in which outcome was reported, all patients fully recovered.

In placebo-controlled clinical trials, ejaculatory disturbance in men was reported in 13% to 28% of men taking paroxetine, compared to 0% to 2% in the placebo group. Decreased libido was reported in 6% to 15% in men treated with paroxetine, compared to 0% to 5% in the placebo group, and in 0% to 9% in women treated with paroxetine, compared with 0% to 2% in placebo patients. The estimates of the incidence of untoward sexual experience and performance may underestimate their actual incidence, partly because patients and physicians may be reluctant to discuss this issue.[Ref]

Dermatologic

Seven cases of alopecia have been reported. In all cases, hair loss was eventually reversible.

A case of cutaneous leukocytoclastic vasculitis has been reported following treatment with paroxetine (the active ingredient contained in Paxil CR) The patient originally developed the lesions after treatment with escitalopram. The lesions disappeared one week following discontinuation of escitalopram and reappeared upon rechallenge. When the patient was switched to paroxetine a similar reaction occurred.[Ref]

Endocrine

Gastrointestinal

A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed up to 3.2 times more frequently in patients receiving paroxetine (the active ingredient contained in Paxil CR) [Ref]

In placebo-controlled clinical trials patients receiving paroxetine experienced abnormal values on liver function tests at a rate equal to or less than that reported in patients receiving placebo. However, there have been postmarketing reports of patients developing elevated serum transaminases resulting in severe liver dysfunction, as well as, a few cases of elevated liver function tests resulting in death secondary to liver necrosis.[Ref]